When your healthcare provider tests for potential toxicity, he or she will get results to help administer
5-FU/capecitabine therapy with the aim of reducing toxicity and increasing effectiveness.
Variations in 2 genes, DPYD and TYMS, are responsible for a significant portion of serious side effects to 5-FU/capecitabine–based therapy.1-5
TheraGuide 5-FU™ provides comprehensive analysis of the DPYD and TYMS genes to identify high-risk individuals and help reduce or prevent toxicity in patients being considered for 5-FU/capecitabine–based therapy.
Overview of Results
Certain variations in the DPYD and TYMS genes are associated with up to a 60% risk of dose-limiting toxicity to 5-FU/capecitabine–based therapies. Patients carrying these variations should be managed differently, taking into account their high-risk status for side effects to 5-FU. Possible results from testing include:
HIGH RISK
- A positive result for a clinically significant genetic variation that increases the risk of toxicity by up to 60%
MODERATE RISK
- A positive result for a clinically significant variation in TYMS.
LOW RISK*
- No mutation is detected and no increased risk of toxicity is expected due to genetic variations in the DPYD or TYMS genes
INDETERMINATE RESULT
- A genetic variation of uncertain significance is detected, but the associated toxicity risk is unknown
Once your healthcare provider receives your results, he or she will be able to integrate them into your management plan and develop a regimen that's individualized for you.
*Risks reported are only those associated with detectable variations in the DPYD and TYMS genes. There may be other, less common factors that affect risk for toxicity.
References: 1. Morel A, Boisdron-Celle M, Fey L, et al. Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther. 2006;5:2895-2904. 2. Pullarkat ST, Stoehlmacher J, Ghaderi V, et al. Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J. 2001;1:65-70. 3. Lecomte T, Ferraz J-M, Zinzindohoué F, et al. Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. Clin Cancer Res. 2004;10:5880-5888. 4. Ichikawa W, Takahashi T, Suto K, et al. Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen. Clin Cancer Res. 2006;12:3928-3934. 5. Schwab M, et al. Role of genetic and non-genetic factors for fluorouracil treatment related severe toxicity; a prospective clinical trial by the German 5-FU toxicity study group. J Clin Oncol, 2008.
